Maintenance Treatment of Depression in Old Age: A Randomized, Double-blind, Placebo-Controlled Evaluation of the Efficacy and Safety of Donepezil Combined with Antidepressant Pharmacotherapy

Details

• Alternative Title:
  Arch Gen Psychiatry
• Personal Author:
  Reynolds, Charles F. ; Butters, Meryl A. ; Lopez, Oscar ; Pollock, Bruce G. ; Dew, Mary Amanda ; Mulsant, Benoit H. ; Lenze, Eric J. ; Holm, Margo ; Rogers, Joan C. ; Mazumdar, Sati ; Houck, Patricia R. ; Begley, Amy ; Anderson, Stewart ; Karp, Jordan F. ; Miller, Mark D. ; Whyte, Ellen M. ; Stack, Jacqueline ; Gildengers, Ariel ; Szanto, Katalin ; Bensasi, Salem ; Kaufer, Daniel I. ; Kamboh, M. Ilyas ; DeKosky, Steven T.
• Description:
  Context
  
  Cognitive impairment in late-life depression is a core feature of the illness.
  
  Objective
  
  to test whether donepezil + antidepressant is superior to placebo + antidepressant in (1) improving cognitive performance and instrumental activities of daily living and (2) reducing recurrences of depression over two years of maintenance treatment.
  
  Design
  
  Randomized, double-blind, placebo controlled maintenance trial.
  
  Setting
  
  university clinic
  
  Main Outcome Measures
  
  global neuropsychological performance, cognitive instrumental ADL, and recurrent depression.
  
  Results
  
  Donepezil + antidepressant temporarily improved global cognition (treatment by time interaction F = 3.78, df = 2, 126, p = .03), but effect sizes were small (Cohen’s d = 0.27: group difference at 1 year). A marginal benefit to cognitive instrumental ADL was also observed (treatment by time interaction; F = 2.94; df = 2, 137, p = 0.06). The donepezil group was more likely to experience recurrent major depression: 35% [95% CI: 24%, 46%] versus 19% [95% CI: 9%, 29%] (log rank chi squared = 3.97, p = .05); hazard ratio = 2.09 [95% CI: 1.00, 4.41]. Post-hoc subgroup analyses showed that, of 57 participants with mild cognitive impairment, 3/30 on donepezil (10%; 95% CI: 0, 21%) and 9/27 on placebo (33%; 95% CI: 16%, 51%) converted to dementia over two years (Fisher exact p = 0.05). The MCI subgroup had a 44 percent recurrence rate of major depression on donepezil verses 12% on placebo (LR=4.91, p=.03). The subgroup with normal cognition (n = 73) showed no benefit on donepezil or increase in recurrence of major depression.
  
  Conclusion
  
  Whether ChEI should be used as augmentation in the maintenance treatment of late-life depression depends upon a careful weighing of risks and benefits in those with MCI. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to MCI/dementia or recurrence of depression.
  
  
• Subjects:
  Activities Of Daily Living Aged Aged, 80 And Over Aging Antidepressive Agents Cholinesterase Inhibitors Cognition Depressive Disorder, Major Donepezil Double-Blind Method Drug Therapy, Combination Female Follow-Up Studies Humans Indans Male Nootropic Agents Piperidines Secondary Prevention Treatment Outcome

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• Source:
  Arch Gen Psychiatry. 68(1):51-60
• Pubmed ID:
  21199965
• Pubmed Central ID:
  PMC3076045
• Document Type:
  Journal Article
• Funding:
  UL1 TR000005/TR/NCATS NIH HHSUnited States/ ; R01 AG022462/AG/NIA NIH HHSUnited States/ ; R01 MH037869-25/MH/NIMH NIH HHSUnited States/ ; R01 MH043823/MH/NIMH NIH HHSUnited States/ ; R01 MH043832-16A1/MH/NIMH NIH HHSUnited States/ ; P30 MH071944/MH/NIMH NIH HHSUnited States/ ; P50 AG005133/AG/NIA NIH HHSUnited States/ ; K01 EB009724/EB/NIBIB NIH HHSUnited States/ ; P50 AG05133/AG/NIA NIH HHSUnited States/ ; R01 AG030653/AG/NIA NIH HHSUnited States/ ; R01 MH037869/MH/NIMH NIH HHSUnited States/ ; P30 MH071944-05/MH/NIMH NIH HHSUnited States/ ; R49 CE001495/CE/NCIPC CDC HHSUnited States/ ; R21 AG033387/AG/NIA NIH HHSUnited States/ ; R01 MH043832/MH/NIMH NIH HHSUnited States/ ; P50 AG005133-24/AG/NIA NIH HHSUnited States/ ; R01 MH083660/MH/NIMH NIH HHSUnited States/ ; R01MH072947/MH/NIMH NIH HHSUnited States/ ; AG030653/AG/NIA NIH HHSUnited States/ ; R01 AG030653-03/AG/NIA NIH HHSUnited States/ ; R01 MH072947-05S1/MH/NIMH NIH HHSUnited States/ ; R01 MH072947/MH/NIMH NIH HHSUnited States/ ; KL2 TR000146/TR/NCATS NIH HHSUnited States/
• Volume:
  68
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:1189011cc35d193ba7869a69b3f341f84eac323dc41c747fe836a847800ca6c2
• Download URL:
  https://stacks.cdc.gov/view/cdc/41827/cdc_41827_DS1.pdf
• File Type:
  [PDF - 828.42 KB ]